PREVALENCE OF UNKNOWN DIABETES AND IMPAIRED GLUCOSE TOLERANCE IN PATIENTS WITH IMPAIRED FASTING GLUCOSE

There are many community-based studies on the prevalence of diabetes, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). However, studies on the prevalence of IGT and diabetes unknown in patients with IFG, by 75-g oral glucose tolerance test (OGTT), are few and small.CIBEROBN is an Instituto de Salud Carlos III initiative. This work has been co-financied by CIBEROBN, Research Grants of the Ministerio de Economía y Competitividad of Spain (Instituto de Salud Carlos III: PI10/00913), and Consejería de Salud de la Junta de Andalucía of Spain (PI-0037/2008 and PI-0112-2013).Peer Reviewe

The Mediterranean diet protects against waist circumference enlargement in 12Ala carriers for the PPARgamma gene: 2 years' follow-up of 774 subjects at high cardiovascular risk.

The PPARgamma gene regulates insulin sensitivity and adipogenesis. The Pro12Ala polymorphism of this gene has been related to fat accumulation. Our aim was to analyse the effects of a 2-year nutritional intervention with Mediterranean-style diets on adiposity in high-cardiovascular risk patients depending on the Pro12Ala polymorphism of the PPARgamma gene. The population consisted of a substudy (774 high-risk subjects aged 55-80 years) of the Prevención con Dieta Mediterránea (PREDIMED) randomised trial aimed at assessing the effect of the Mediterranean diet for CVD prevention. There were three nutritional intervention groups: two of them of a Mediterranean-style diet and the third was a control group advised to follow a conventional low-fat diet. All the participants were genotyped by PCR-restriction fragment length polymorphism (RFLP). The results showed that carriers of the 12Ala allele allocated to the control group had a statistically significant higher change in waist circumference (adjusted difference coefficient = 2.37 cm; P = 0.014) compared with wild-type subjects after 2 years of nutritional intervention. This adverse effect was not observed among 12Ala carriers allocated to both Mediterranean diet groups. In diabetic patients a statistically significant interaction between Mediterranean diet and the 12Ala allele regarding waist circumference change was observed ( - 5.85 cm; P = 0.003). In conclusion, the Mediterranean diet seems to be able to reduce waist circumference in a high-cardiovascular risk population, reversing the negative effect that the 12Ala allele carriers of the PPARgamma gene appeared to have. The beneficial effect of this dietary pattern seems to be higher among type 2 diabetic subjects

Fruit and vegetable consumption is inversely associated with plasma saturated fatty acids at baseline in PREDIMED plus trial

Scope: Plasma fatty acids (FAs) are associated with the development of cardiovascular diseases and metabolic syndrome. The aim of our study is to assess the relationship between fruit and vegetable (F&V) consumption and plasma FAs and their subtypes. Methods and Results: Plasma FAs are assessed in a cross-sectional analysis of a subsample of 240 subjects from the PREDIMED-Plus study. Participants are categorized into four groups of fruit, vegetable, and fat intake according to the food frequency questionnaire. Plasma FA analysis is performed using gas chromatography. Associations between FAs and F&V consumption are adjusted for age, sex, physical activity, body mass index (BMI), total energy intake, and alcohol consumption. Plasma saturated FAs are lower in groups with high F&V consumption (-1.20 mg cL−1 [95% CI: [-2.22, - 0.18], p-value = 0.021), especially when fat intake is high (-1.74 mg cL−1 [95% CI: [-3.41, -0.06], p-value = 0.042). Total FAs and n-6 polyunsaturated FAs tend to be lower in high consumers of F&V only in the high-fat intake groups. Conclusions: F&V consumption is associated with lower plasma saturated FAs when fat intake is high. These findings suggest that F&V consumption may have different associations with plasma FAs depending on their subtype and on the extent of fat intake

High fruit and vegetable consumption and moderate fat intake are associated with higher carotenoid concentration in human plasma

Carotenoids are pigments contained mainly in fruit and vegetables (F&V) that have bene ficial effects on cardiometabolic health. Due to their lipophilic nature, co-ingestion of fat appears to increase their bioavailability via facilitating transfer to the aqueous micellar phase during diges tion. However, the extent to which high fat intake may contribute to increased carotenoid plasma concentrations is still unclear. The objective was to examine the degree to which the consumption of different amounts of both carotenoid-rich foods and fats is associated with plasma carotenoid concentrations within a Mediterranean lifestyle context (subsample from the PREDIMED-Plus study baseline) where consumption of F&V and fat is high. The study population was catego rized into four groups according to their self-reported consumption of F&V and fat. Carotenoids were extracted from plasma samples and analyzed by HPLC-UV-VIS-QqQ-MS/MS. Carotenoid systemic concentrations were greater in high consumers of F&V than in low consumers of these foods (+3.04 µmol/L (95% CI: 0.90, 5.17), p-value = 0.005), but circulating concentrations seemed to decrease when total fat intake was very high (−2.69 µmol/L (−5.54; 0.16), p-value = 0.064). High consumption of F&V is associated with greater systemic levels of total carotenoids, in particular when fat intake is low-to-moderate rather than very high

Quality of dietary fat intake and body weight and obesity in a Mediterranean population: Secondary analyses within the PREDIMED trial

A moderately high-fat Mediterranean diet does not promote weight gain. This study aimed to investigate the association between dietary intake of specific types of fat and obesity and body weight. A prospective cohort study was performed using data of 6942 participants in the PREDIMED trial, with yearly repeated validated food-frequency questionnaires, and anthropometric outcomes (median follow-up: 4.8 years). The effects of replacing dietary fat subtypes for one another, proteins or carbohydrates were estimated using generalized estimating equations substitution models. Replacement of 5% energy from saturated fatty acids (SFA) with monounsaturated fatty acids (MUFA) or polyunsaturated fatty acids (PUFA) resulted in weight changes of −0.38 kg (95% Confidece Iinterval (CI): −0.69, −0.07), and −0.51 kg (95% CI: −0.81, −0.20), respectively. Replacing proteins with MUFA or PUFA decreased the odds of becoming obese. Estimates for the daily substitution of one portion of red meat with white meat, oily fish or white fish showed weight changes up to −0.87 kg. Increasing the intake of unsaturated fatty acids at the expense of SFA, proteins, and carbohydrates showed beneficial effects on body weight and obesity. It may therefore be desirable to encourage high-quality fat diets like the Mediterranean diet instead of restricting total fat intake

Radiation tests on commercial instrumentation amplifiers, analog switches & DAC's

A study of several commercial instrumentation amplifiers (INA110, INA111, INA114, INA116, INA118 & INA121) under neutron and vestigial gamma radiation was done. Some parameters (Gain, input offset voltage, input bias currents) were measured on-line and bandwidth, and slew rate were determined before and after radiation. The results of the testing of some voltage references REF102 and ADR290GR and the DG412 analog switch are shown. Finally, different digital-to-analog converters were tested under radiation

Fiber intake and all-cause mortality in the Prevención con Dieta Mediterránea (PREDIMED) study

Background: Few observational studies have examined the effect of dietary fiber intake and fruit and vegetable consumption on total mortality and have reported inconsistent results. All of the studies have been conducted in the general population and typically used only a single assessment of diet. Objective: We investigated the association of fiber intake and whole-grain, fruit, and vegetable consumption with all-cause mortality in a Mediterranean cohort of elderly adults at high cardiovascular disease (CVD) risk by using repeated measurements of dietary information and taking into account the effect of a dietary intervention. Design: We followed up 7216 men (55-75 y old) and women (60-75 y old) at high CVD risk in the Prevención con Dieta Mediterránea (PREDIMED) trial for a mean of 5.9 y. Data were analyzed as an observational cohort. Participants were initially free of CVD. A 137-item validated food-frequency questionnaire administered by dietitians was repeated annually to assess dietary exposures (fiber, fruit, vegetable, and whole-grain intakes). Deaths were identified through the continuing medical care of participants and the National Death Index. An independent, blinded Event Adjudication Committee adjudicated causes of death. Cox regression models were used to estimate HRs of death during follow-up according to baseline dietary exposures and their yearly updated changes. Results: In up to 8.7 y of follow-up, 425 participants died. Baseline fiber intake and fruit consumption were significantly associated with lower risk of death [HRs for the fifth compared with the first quintile: 0.63 (95% CI: 0.46, 0.86; P = 0.015) and 0.59 (95% CI: 0.42, 0.82; P = 0.004), respectively]. When the updated dietary information was considered, participants with fruit consumption .210 g/d had 41% lower risk of all-cause mortality (HR: 0.59; 95% CI: 0.44, 0.78). Associations were strongest for CVD mortality than other causes of death. Conclusion: Fiber and fruit intakes are associated with a reduction in total mortality. PREDIMED was registered at controlled-trials.com as ISRCTN35739639. © 2014 American Society for Nutrition.Peer Reviewe

Mitochondrial dysfunction: a common hallmark underlying comorbidity between sIBM and other degenerative and age-related diseases

Sporadic inclusion body myositis (sIBM) is an inflammatory myopathy associated, among others, with mitochondrial dysfunction. Similar molecular features are found in Alzheimer's disease (AD) and Type 2 Diabetes Mellitus (T2DM), underlying potential comorbidity. This study aims to evaluate common clinical and molecular hallmarks among sIBM, AD, and T2DM. Comorbidity with AD was assessed in n = 14 sIBM patients by performing neuropsychological and cognitive tests, cranial magnetic resonance imaging, AD cerebrospinal fluid biomarkers (levels of amyloid beta, total tau, and phosphorylated tau at threonine-181), and genetic apolipoprotein E genotyping. In the same sIBM cohort, comorbidity with T2DM was assessed by collecting anthropometric measures and performing an oral glucose tolerance test and insulin determinations. Results were compared to the standard population and other myositis (n = 7 dermatomyositis and n = 7 polymyositis). Mitochondrial contribution into disease was tested by measurement of oxidative/anaerobic and oxidant/antioxidant balances, respiration fluxes, and enzymatic activities in sIBM fibroblasts subjected to different glucose levels. Comorbidity of sIBM with AD was not detected. Clinically, sIBM patients showed signs of misbalanced glucose homeostasis, similar to other myositis. Such misbalance was further confirmed at the molecular level by the metabolic inability of sIBM fibroblasts to adapt to different glucose conditions. Under the standard condition, sIBM fibroblasts showed decreased respiration (0.71 ± 0.08 vs. 1.06 ± 0.04 nmols O2/min; p = 0.024) and increased anaerobic metabolism (5.76 ± 0.52 vs. 3.79 ± 0.35 mM lactate; p = 0.052). Moreover, when glucose conditions were changed, sIBM fibroblasts presented decreased fold change in mitochondrial enzymatic activities (−12.13 ± 21.86 vs. 199.22 ± 62.52 cytochrome c oxidase/citrate synthase ratio; p = 0.017) and increased oxidative stress per mitochondrial activity (203.76 ± 82.77 vs. −69.55 ± 21.00; p = 0.047), underlying scarce metabolic plasticity. These findings do not demonstrate higher prevalence of AD in sIBM patients, but evidences of prediabetogenic conditions were found. Glucose deregulation in myositis suggests the contribution of lifestyle conditions, such as restricted mobility. Additionally, molecular evidences from sIBM fibroblasts confirm that mitochondrial dysfunction may play a role. Monitoring T2DM development and mitochondrial contribution to disease in myositis patients could set a path for novel therapeutic options

Mesoscopic effects in an agent-based bargaining model in regular lattices

The effect of spatial structure has been proved very relevant in repeated games. In this work we propose an agent based model where a fixed finite population of tagged agents play iteratively the Nash demand game in a regular lattice. The model extends the multiagent bargaining model by Axtell, Epstein and Young [1] modifying the assumption of global interaction. Each agent is endowed with a memory and plays the best reply against the opponent’s most frequent demand. We focus our analysis on the transient dynamics of the system, studying by computer simulation the set of states in which the system spends a considerable fraction of the time. The results show that all the possible persistent regimes in the global interaction model can also be observed in this spatial version. We also find that the mesoscopic properties of the interaction networks that the spatial distribution induces in the model have a significant impact on the diffusion of strategies, and can lead to new persistent regimes different from those found in previous research. In particular, community structure in the intratype interaction networks may cause that communities reach different persistent regimes as a consequence of the hindering diffusion effect of fluctuating agents at their borders.Spanish Ministry of Science and Innovation, references TIN2008-06464-C03-02 and CSD2010-00034 (CONSOLIDER-INGENIO 2010), and by the Junta de Castilla y Leon, references VA006A009, BU034A08 and GREX251-200

Unraveling Inclusion Body Myositis Using a Patient-derived Fibroblast Model

Background: Inclusion body myositis (IBM) is an inflammatory myopathy clinically characterized by proximal and distal muscle weakness, with inflammatory infiltrates, rimmed vacuoles and mitochondrial changes in muscle histopathology. There is scarce knowledge on IBM aetiology, and non-established biomarkers or effective treatments are available, partly due to the lack of validated disease models. Methods: We have performed transcriptomics and functional validation of IBM muscle pathological hallmarks in fibroblasts from IBM patients (n = 14) and healthy controls (n = 12), paired by age and sex. The results comprise an mRNA-seq, together with functional inflammatory, autophagy, mitochondrial and metabolic changes between patients and controls. Results: Gene expression profile of IBM vs control fibroblasts revealed 778 differentially expressed genes (P-value adj < 0.05) related to inflammation, mitochondria, cell cycle regulation and metabolism. Functionally, an increased inflammatory profile was observed in IBM fibroblasts with higher supernatant cytokine secretion (three-fold increase). Autophagy was reduced considering basal protein mediators (18.4% reduced), time-course autophagosome formation (LC3BII 39% reduced, P-value < 0.05), and autophagosome microscopic evaluation. Mitochondria displayed reduced genetic content (by 33.9%, P-value < 0.05) and function (30.2%-decrease in respiration, 45.6%-decline in enzymatic activity (P-value < 0.001), 14.3%-higher oxidative stress, 135.2%-increased antioxidant defence (P-value < 0.05), 11.6%-reduced mitochondrial membrane potential (P-value < 0.05) and 42.8%-reduced mitochondrial elongation (P-value < 0.05)). In accordance, at the metabolite level, organic acid showed a 1.8-fold change increase, with conserved amino acid profile. Correlating to disease evolution, oxidative stress and inflammation emerge as potential markers of prognosis. Conclusions: These findings confirm the presence of molecular disturbances in peripheral tissues from IBM patients and prompt patients’ derived fibroblasts as a promising disease model, which may eventually be exported to other neuromuscular disorders. We additionally identify new molecular players in IBM associated with disease progression, setting the path to deepen in disease aetiology, in the identification of novel biomarkers or in the standardization of biomimetic platforms to assay new therapeutic strategies for preclinical studies